Sodium-sensitive hypertension is associated with an intrinsic or imposed aberration in renal function which results in the retention of sodium. A model is proposed in which the accumulated sodium is responsible for the activation of the central nervous system to stimulate sympathetic nervous system activity. This increase in sympathetic outflow causes an elevation in total peripheral resistance including renal vascular resistance. The increased renal vascular resistance results in a further retention of sodium creating a positive feedback loop on the central nervous system. With continued sympathetic stimulation, arterial pressure rises increasing renal perfusion pressure and reestablishing sodium balance. In other words, the arterial pressure-sodium excretion relationship is shifted to a higher arterial pressure. Thus, the central hypothesis to be examined in this proposal is that sodium retention causes an activation of the sympathetic nervous system and increase in regional vascular resistance. To evaluate this model, three specific hypotheses will be tested. The first study will investigate the postulate that increasing amounts of sodium intake will cause a proportional elevation in regional sympathetic outflow (as determined by measurements of norepinephrine turnover rate) and regional vascular resistance (as estimated by Doppler flowprobes on the renal, iliac and mesenteric arteries). Accordingly, sodium depletion will open the feedback loop proposed in the model and prevent the hypertension. The second study will test the hypothesis that interruption of sympathetic outflow to the kidneys by renal denervation will prevent the development of hypertension by interfering with the increase in renal norepinephrine turnover rate and subsequent rise in vascular resistance. Thus, the retention of sodium will be prevented. The final study will examine directly the hypothesis that the increased renal vascular resistance is associated with a retention of sodium. The role of the renal nerves in this process will be determined by studying a group of renal denervated rats. These studies will provide a foundation for understanding the relationship between sodium-induced hypertension and hemodynamic changes associated with the activation of the sympathetic nervous system. The information gained will provide significant insights into the sequence of events comprising the hypertensive process.